106(P-60) ジョルキノライドDファーマコホア : 合成とアミノ酸、ヌクレオシドおよびDNAに対する反応性(ポスター発表の部)

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Jolkinolide D (1) is a diterpenoid isolated from Euphorbia jolkini Boiss in 1974, and its stereostructure was recently determined by X-ray crystallographic analysis. It inhibited tumor invasion into the basement membrane and induced apoptosis in tumor cells. Jolkinolide D (1) has a γ,δ-unsaturated-β-hydroxy-α-methylene lactone unit as the pharmacophore structure, which suggests that jolkinolide D (1) might alkylate biomolecules such as proteins and DNA irreversibly. Since there are no other compounds that have the pharmacophore, reactivities of the unit toward nucleophiles have not hitherto been investigated. For the purpose of obtaining preliminary information on the chemical modification of biomolecules with jolkinolide D (1), jolkinolide D pharmacophore (2) was synthesized from 6-(tert-butyldimethylsilyloxy)-3-methyl-2-cyclohexenone (3) and 2-iodoallylalcohol (4), and its reactivity toward amino acids, nucleosides, and DNA was investigated. It was found that the order of reactivity of jolkinolide D pharmacophore (2) toward the nucleophiles in the amino acids at pH 7.5 is the thiol group in L-cysteine and glutathione > the imidazolyl group in L-histidine, the α-amino groups in amino acids > the carboxyl groups in amino acids. Jolkinolide D pharmacophore (2) alkylated 2'-deoxyguanosine at the N-1 position (pH 7.5) and thymidine at the N-3 position (pH 8.7), and modified DNA at the same sites in lower yields.
天然有機化合物討論会の論文
2002-09-01

106(P-60) ジョルキノライドDファーマコホア : 合成とアミノ酸、ヌクレオシドおよびDNAに対する反応性(ポスター発表の部)

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